Bis(2-oxo-3-oxazolidinyl)phosphinic chloride → {3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone

HRID 2388965노트

반응식

HRID 2388965 반응식
[Cl:1][C:2]1[C:3]([OH:28])=[C:4]([CH:8]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[N:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:10]=1)[C:5]([OH:7])=O.[CH2:29]([N:31]([CH2:40][CH3:41])[CH2:32][CH2:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)[CH3:30].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.C(=O)(O)[O-].[Na+]>C(#N)C.CN(C=O)C.O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([OH:28])=[C:4]([C:5]([N:37]2[CH2:38][CH2:39][N:34]([CH2:33][CH2:32][N:31]([CH2:40][CH3:41])[CH2:29][CH3:30])[CH2:35][CH2:36]2)=[O:7])[CH:8]=[C:9]([C:11]2[CH:12]=[C:13]3[C:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[O:26][CH3:27])=[N:18][NH:17][C:14]3=[N:15][CH:16]=2)[CH:10]=1

참가 물질

9

반응물 4

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride2회HCID 516892Sodium BicarbonateHCID 2736105N,N-Diethyl-2-(piperazin-1-yl)ethan-1-amineHCID 1784893953-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzoic acid

생성물 1

HCID 178464031{3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone수율 17%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

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온도
75 °C

실험 절차

14 mg (35 mol) of 3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzoic acid and 22 μL (approx. 120 μmol; density unknown) of 1-(2-diethylaminoethyl)-piperazine were dissolved in a mixture of 1 mL of acetonitrile and 100 μL of DMF. 14 mg (55 μmol) of bis(2-oxo-3-oxazolidinyl)phosphinic chloride was added and the mixture heated gently until all materials were dissolved. The resulting solution was left at ambient temperature for 4.5 h. 28 mg (110 μmol) of bis(2-oxo-3-oxazolidinyl)phosphinic chloride was added and the resulting mixture left at ambient temperature for 3.5 h, then heated to 75° C. for 3.5 h. The resulting mixture was distributed between 1 mL of a saturated aqueous solution of sodium bicarbonate in water and 2 mL of ethyl acetate. The organic phase was evaporated and the residue directly purified by mass-triggered reverse-phase HPLC to afford 3.2 mg (5.7 μmol, 17%) of {3-chloro-2-hydroxy-5-[3-(2-methoxy-phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-[4-(2-diethylamino-ethyl)-piperazin-1-yl]-methanone as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ 13.80 (s, br. 1H), 8.81 (d, 1H), 8.29 (d, 1H), 7.82 (d, 1H), 7.64 (dd, 1H), 7.49-7.44 (m, 2H), 7.21 (d, 1H), 7.10 (ddd, 1H), 3.83 (s, 3H), 3.40-3.30 (m, 4H), 2.49-2.35 (m, 8H), 0.94 (t, 6H), MS: m/z 563.2 (M+H+).

후처리

  1. temperaturethe mixture heated gently until all materials
  2. dissolutionwere dissolved
  3. waitthe resulting mixture left at ambient temperature for 3.5 h
  4. customThe organic phase was evaporated
  5. customthe residue directly purified by mass-triggered reverse-phase HPLC

출처 및 근거

ORD 기록
ord-d77df84cb25d45bd9012e4da0017fd46
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268994B2

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